Endophilins

Endophilins are a family of membrane remodeling proteins that participate in clathrin-mediated endocytosis and intracellular trafficking. They contain an N-terminal BAR (BIN/amphiphysin/Rvs) domain that forms a curved dimer capable of binding and bending membranes, an adjacent amphipathic helix that enhances curvature sensing, and a C-terminal SH3 domain that mediates interactions with proline-rich motifs in partner proteins. This domain architecture enables endophilins to promote membrane curvature and coordinate vesicle formation.

In endocytosis, endophilins are recruited to sites of vesicle formation where they facilitate membrane remodeling and coordinate vesicle scission. The SH3 domain binds proline-rich partners such as dynamin, synaptojanin, intersectin, and N-WASP, linking curvature generation with the scission machinery. Endophilin A proteins are particularly important in neuronal synaptic vesicle recycling, where they regulate rapid endocytosis after neurotransmitter release. Endophilins also interact with lipids, including phosphoinositides, which helps target them to the plasma membrane and endosomal membranes.

Vertebrates express three Endophilin A isoforms (A1, A2, A3; gene names SH3GL1-3) and three Endophilin B isoforms (B1-3; SH3GLB1-3). Endophilin A1 is enriched in brain tissue, whereas members of the B family participate more broadly in endosomal sorting and intracellular trafficking. The specific functions of B isoforms remain less well defined but are linked to membrane trafficking and autophagy through SH3-mediated interactions and coordination with other endocytic proteins.

Dysregulation of endophilins can impair endocytosis and synaptic function, with potential implications for neurological disorders. See also clathrin-mediated endocytosis, dynamin, and synaptojanin.